Hypertension is a common cardiovascular disease, the main clinical syndrome of which is the arterial pressure is elevated persistently, and it often causes lesions of the heart, brain, kidneys and other vital organs and the corresponding consequences. China is one of the countries affected by hypertension in the world. In the past few decades, the estimated number adults with hypertension has increased from 30 million in 1960 to 59 million in 1980, and reached to 94 million people in 1991. The number is more than 200 million currently. Among the 3 million cardiovascular patients that die every year, 50% are associated with hypertension. In the United States, ⅓ of adults are suffering from hypertension. It is extremely urgent to develop effective antihypertensive drugs with less adverse reactions.
According to the mechanism of the drug, conventional antihypertensive drugs can be classified into central antihypertensive drugs, ganglion blockers, sympathetic nerve endings inhibitors, adrenergic blockers, vasodilators, diuretics, angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor antagonists. Renin-angiotensin system (RAS) is a group of hormones or precursors interacting or regulating with each other secreted by kidney and liver, including renin, angiotensinogen, angiotensin I (Ang I), angiotensin II (Ang II), angiotensin-converting enzyme (ACE) and angiotensin receptor etc., in which Ang II is one of the strongest vasoconstrictors, having numerous biological activities.
Azilsartan medoxomil (the structure of formula A) is an angiotensin II receptor antagonist drug for treating hypertension developed by Takeda, which belongs to angiotensin II receptor antagonist drug (Sartans). Azilsartan medoxomil potassium salt, Edabi® as the trade name, was approved by the FDA. This drug is an oral medicament which can be used alone or in combination with other antihypertensive agents for the treatment of hypertension and related complications. Azilsartan medoxomil has a more significant effect in lowering blood pressure. Compared with losartan and olmesartan medoxomil, Azilsartan medoxomil is more efficient in reducing blood pressure (WHITE W B. Effects of the angiotensin receptor blocker azilsartan medoxomil versus olmesartan and valsartan on ambulatory and clinic blood pressure in patients with stages 1 and hypertension J. Hypertension, 2011, 57(3):413-420). Azilsartan medoxomil is a pro-drug, which can be rapidly hydrolyzed into Azilsartan and take action during absorption in the gastrointestinal tract. Azilsartan (the structure of formula B), the chemical name of which is 1-[[2′-(4,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl) [1,1′-biphenyl]-4-yl]methyl]-2-ethoxy-1H-benzimidazol-7-carboxylic acid, decreases blood pressure by selectively blocking the binding of angiotensin II to vascular smooth muscle AT1 receptor to block the vasoconstrictive effect of angiotensin II in vivo.

EP1992110668, U.S. Pat. No. 5,243,054A, and US20050187269 disclose the preparation method of Azilsartan and its analogues; Chinese patent CN100503605C discloses Azilsartan medoxomil potassium salt and the preparation and pharmacodynamic effect thereof; WO2010075347 discloses the pharmaceutical application and pharmacological activity of Azilsartan medoxomil and Azilsartan medoxomil potassium salt; CN101381366B discloses Azilsartan and Azilsartan medoxomil potassium salt.
However, subsequent research indicates that as there is a carboxyl group in the molecular structure of the direct active ingredient Azilsartan, the in vivo absorption is poor and it affects the efficacy of the drug, so Azilsartan is not easy to prepare into pharmaceutical dosage forms. In order to improve the bioavailability, Azilsartan has to be prepared into an ester by chemical modification, i.e. Azilsartan medoxomil, but its bioavailability is still not satisfied and its molecular structure becomes complex by such modification, which increases difficulty in synthesis and cost of production.